RBM5 plays important roles in the post-transcriptional regulation of mRNAs that are involved in the metabolism of chemotherapeutic reagents.

RBM5 在参与化疗试剂代谢的 mRNA 转录后调节中发挥重要作用。

• 批准号: 23591007
• 负责人: KAWAKAMI Hiroshi
• 金额: $ 3.41万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591007/
• 关键词: 薬剤耐性; 抗癌剤耐性; 膵癌

Despite recent advances in various chemotherapeutic regimens, pancreatic cancer remains highly resistant to conventional chemotherapy. The putative tunor suppressor RBM5 is known to modulate apoptosis and cell cycle arrest but the molecular mechanisms of RBM5 function are poorly understood.We show here that RBM5 interacted with HuR, which is one of mRNA regulatory proteins that bind AU-rich elements in the 3'-untranslated regions of target mRNAs, stabilizing them and modulating their translation. Certain cell stresses including chemotherapeutic reagents induce translocation of HuR from the nucleus to the cytoplasm. RBM5 associated with HuR in the nucleus and reduced translocation of HuR to the cytoplasm. Furthermore, RBM5 overexpression decreased the association of HuR with target mRNAs.Taken together, we suggest that RBM5 might play important roles in the post-transcriptional regulation of mRNAs that are involved in the metabolism of chemotherapeutic reagents.

尽管最近在各种化疗方案中取得了进展，但胰腺癌仍然对常规化疗具有高度耐药性。我们发现RBM5与HuR相互作用，HuR是一种mRNA调节蛋白，它与靶mRNA 3 '非翻译区富含AU的元件结合，稳定靶mRNA并调节靶mRNA的翻译。某些细胞应激（包括化学治疗剂）诱导HuR从细胞核易位至细胞质。RBM5与细胞核中的HuR相关，并减少HuR向细胞质的易位。此外，RBM5的过表达降低了HuR与靶mRNA的结合。综上所述，我们认为RBM5可能在参与化疗药物代谢的mRNA的转录后调节中发挥重要作用。

项目成果

Human equilibrative nucleoside transporter 1 and Notch3 can predict gemcitabine effects in patients with unresectable pancreatic cancer.

• DOI: 10.1038/bjc.2013.108
• 发表时间: 2013-04-16
• 期刊: British journal of cancer
• 影响因子: 8.8
• 作者: Eto K;Kawakami H;Kuwatani M;Kudo T;Abe Y;Kawahata S;Takasawa A;Fukuoka M;Matsuno Y;Asaka M;Sakamoto N
• 通讯作者: Sakamoto N

切除不能膵癌に対する超音波内視鏡下穿刺吸引生検検体を用いたgemcitabine 感受性予測因子の検討

使用超声内镜引导的细针抽吸活检标本检查不可切除胰腺癌的吉西他滨敏感性预测因子

• 发表时间: 2013
• 作者: Ohshima Y;Yasuda I;Kawakami H;Kuwatani M;Mukai T;Iwashita T;Doi S;Nakashima M;Hirose Y;Asaka M;Moriwaki H.;江藤和範,河上洋,坂本直哉;江藤和範，河上 洋，坂本直哉
• 通讯作者: 江藤和範，河上 洋，坂本直哉

超音波内視鏡下穿刺吸引生検検体を用いた膵癌における抗癌剤感受性予測因子の検討

使用超声内镜引导细针抽吸活检标本检查胰腺癌抗癌药物敏感性的预测因素

• 发表时间: 2012
• 作者: Ohshima Y;Yasuda I;Kawakami H;Kuwatani M;Mukai T;Iwashita T;Doi S;Nakashima M;Hirose Y;Asaka M;Moriwaki H.;江藤和範,河上洋,坂本直哉;江藤和範，河上 洋，坂本直哉;江藤和範,河上洋,坂本直哉
• 通讯作者: 江藤和範,河上洋,坂本直哉

切除不能膵癌に対する超音波内視鏡下穿刺吸引生検検体を用いたgemcitabine感受性予測因子の検討

使用超声内镜引导的细针抽吸活检标本检查不可切除胰腺癌的吉西他滨敏感性预测因子

• 发表时间: 2013
• 作者: Ohshima Y;Yasuda I;Kawakami H;Kuwatani M;Mukai T;Iwashita T;Doi S;Nakashima M;Hirose Y;Asaka M;Moriwaki H.;江藤和範,河上洋,坂本直哉
• 通讯作者: 江藤和範,河上洋,坂本直哉